Retraction: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats.

Editor's AnnouncementIn utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in ratsMasaya Motohashi, Michael F. Wempe, Tomoko Mutou, Yuya Okayama, Norio Kansaku, Hiroyuki Takahashi, Masahiro Ikegami, Masao Asari, Shin Wakui(The Journal of Toxicological Sciences, 41, 195-206, 2016) I have retracted the above paper as Editor-in-Chief of The Journal of Toxicological Sciences since I have serious concerns about it, primarily due to inappropriate authorship on a non-negligible scale.When it was brought to my attention that there was inappropriate authorship in this paper, I contacted the co-authors to confirm this point. I found out that the majority of them considered their listing as co-authors to be inappropriate. In addition, the majority agreed to the retraction of this paper.These facts raise concerns about the paper. From the standpoint of maintaining the integrity of the research community, I felt that such a paper should be retracted at once.Accordingly, I sent a summary of my concerns about the paper to the corresponding author, Dr. Shin Wakui. I also had an online interview with him to discuss this matter. I told Dr. Wakui that inappropriate authorship on a non-negligible scale is a serious problem that raises concerns about the paper.I prepared a draft of this Editor's Announcement and sent it to Dr. Wakui for review prior to revision and release. Although he did not agree to the retraction, I have decided to take this action from the standpoint of maintaining the integrity of the research community.I coordinated my response to this issue with Dr. Akira Naganuma, Editor-in-Chief of Fundamental Toxicological Sciences, a sister journal of The Journal of Toxicological Sciences. Toshiyuki Kaji, Ph.D.Editor-in-ChiefThe Journal of Toxicological Sciences.

A rare case of colorectal metastasis found 8 years and 10 months after gastrectomy for advanced gastric cancer: A case report and literature review.

Colorectal metastasis from gastric cancer is rare and may develop several years after gastric cancer surgery. Therefore, colonoscopic findings provide useful diagnostic information. The present report describes a case of gastric cancer colon metastasis diagnosed 8 years and 10 months after gastrectomy for advanced gastric cancer. A 64-year-old male patient underwent gastrectomy in December 2010 and received chemotherapy for 4 years and 10 months after the surgery. Subsequently, the patient was diagnosed as having colorectal cancer by computed tomography in February 2019. Colonoscopy revealed linitis plastica-like colon stenosis; however, biopsy pathology did not reveal any findings indicating malignancy. Right hemicolectomy was performed, and pathological examination revealed colon metastasis from gastric cancer. The patient received chemotherapy but died of peritoneal carcinomatosis 1 year and 8 months after the colectomy. According to literature, colorectal metastasis from gastric cancer is often attributed to hematogenous metastasis and often exhibits characteristic macroscopic features. Treatments, such as chemotherapy for gastric cancer and/or colorectal resection, are considered effective for gastric cancer colorectal metastasis.

A rare case of Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified, in a patient with ulcerative colitis.

While colorectal cancer is a likely complication associated with inflammatory bowel diseases such as ulcerative colitis, malignant lymphoma occurs less frequently. We report the case of a patient with ulcerative colitis having Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV + DLBCL, NOS), which was maintained in clinical remission with 5-aminosalicylic acid. The patient had received a diagnosis of total ulcerative colitis 5 years ago. A recent colonoscopy revealed a 35 mm protruding lesion with depression in the sigmoid colon, and histopathological examination confirmed the presence of EBV + DLBCL, NOS. The patient has undergone six courses of chemotherapy without recurrence of lymphoma and will continue to be monitored periodically. Patients with ulcerative colitis must be followed up with periodic colonoscopies and imaging studies regardless of their background, treatment, and symptoms to ensure the prevention of complications. Furthermore, while special attention must be paid to the commonly occurring colorectal cancer on account of its association with the patient's prognosis, the possibility of the incidence of malignant lymphoma must not be ignored.

ROCK2-induced metabolic rewiring in diabetic podocytopathy.

Loss of podocytes is a common feature of diabetic renal injury and a key contributor to the development of albuminuria. We found that podocyte Rho associated coiled-coil containing protein kinase 2 (ROCK2) is activated in rodent models and patients with diabetes. Mice that lacked ROCK2 only in podocytes (PR2KO) were resistant to albuminuria, glomerular fibrosis, and podocyte loss in multiple animal models of diabetes (i.e., streptozotocin injection, db/db, and high-fat diet feeding). RNA-sequencing of ROCK2-null podocytes provided initial evidence suggesting ROCK2 as a regulator of cellular metabolism. In particular, ROCK2 serves as a suppressor of peroxisome proliferator-activated receptors α (PPARα), which rewires cellular programs to negatively control the transcription of genes involved in fatty acid oxidation and consequently induce podocyte apoptosis. These data establish ROCK2 as a nodal regulator of podocyte energy homeostasis and suggest this signaling pathway as a promising target for the treatment of diabetic podocytopathy.

S100-stained perineural invasion is associated with worse prognosis in stage I/II colorectal cancer: Its possible association with immunosuppression in the tumor.

Perineural invasion (PNI) is known as a poor prognostic factor in colorectal cancer (CRC). Although histopathological evaluation of PNI is usually conducted on hematoxylin and eosin (HE)-stained sections (HE-PNI), it remains controversial whether PNI can be precisely evaluated only by HE-staining, and its concise mechanisms causing worse prognosis remains elusive. In this study, we examined the impact of PNI evaluated by S-100-immunostaining (S100-PNI) on postoperative mortality in 279 consecutive CRC patients and further investigated its association with the tumor immune microenvironment. S100-PNI was present in 67.3% of tumors whereas HE-PNI was present in 18.5%. A 5-year cumulative incidence of death in the S100-PNI-positive group was significantly higher than that in the S100-PNI-negative group. Further statistical analyses revealed that S100-PNI was an independent prognostic factor of all-cause mortality in stage I/II but not in stage III/IV. Importantly, S100-PNI was associated with the altered tumor immune microenvironment. Infiltrating immune cell profiling revealed that stromal lymphocytic reaction, which was inversely correlated with postoperative mortality, was significantly reduced in S100-PNI-positive tumors compared to S100-PNI-negative tumors in stage I/II. These results indicated that S100-PNI was a poor prognostic factor in stage I/II CRC with possible association with immunosuppression in the tumor.

Prostaglandin E-major urinary metabolite diagnoses mucosal healing in patients with ulcerative colitis in remission phase.

BACKGROUND AND AIM: Ulcerative colitis (UC) is usually detected by clinical symptoms, such as bleeding and diarrhea; however, it is rather difficult to assess during asymptomatic clinical remission (CR). Hence, there is a need for a biomarker that can reliably detect UC during remission. We previously reported on the utility of the prostaglandin E-major urinary metabolite (PGE-MUM) as a biomarker reflecting UC activity. In this study, we evaluated the effectiveness of the PGE-MUM in the diagnosis of endoscopic, histological, and histo-endoscopic mucosal remission of UC, comparing with fecal tests. METHODS: This prospective study was conducted at the Jikei University Hospital between August 2017 and January 2021. Patients with UC in CR scheduled to undergo colonoscopy were included. The association between the PGE-MUM with endoscopic remission (ER), histological remission (HR), and complete mucosal healing (CMH, defined as histo-endoscopic remission) was analyzed. We also compared the area under the curve (AUC) for the receiver operating characteristic curves between PGE-MUM, fecal calprotectin (FC), and fecal immunochemical test (FIT). RESULTS: In total, 128 patients were analyzed. PGE-MUM differed significantly in ER versus non-ER (14.5 vs 16.7, P = 0.028), HR versus non-HR (14.2 vs 17.4, P = 0.004), and CMH versus non-CMH (14.3 vs 16.7, P = 0.021). There were no significant differences between the AUCs for PGE-MUM, FC, and FIT for ER, HR, or CMH. CONCLUSIONS: The PGE-MUM can determine CMH in UC even during CR, regardless of the disease phenotype, indicating its clinical benefit for non-invasive monitoring.

The essential problem of over-measuring the depth of submucosal invasion in pT1 colorectal cancer.

A depth of submucosal invasion (DSI) of ≥1000 µm is an important risk factor for lymph node metastasis (LNM) in patients with submucosal invasive (pT1) colorectal cancer (CRC), according to the European Society of Gastrointestinal Endoscopy and the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines. According to the latter, if the location of the muscularis mucosae in the invasive area is not confirmed, the DSI can be measured from the surface. In these cases, a 'remaining intramucosal lesion' (rIL), which is in the invasive area, is sometimes observed. To avoid over-measuring the DSI, we proposed a 'modified DSI' (mDSI), which excludes the rIL from the JSCCR DSI. We investigated the characteristics and effectiveness of the rIL and mDSI by grouping cases with polypoid growth (PG) and non-polypoid growth (NPG) histologically. Three hundred and thirty-nine consecutive patients with pT1 CRC were examined. LNM was detected in 37 cases. The distribution of the DSI and rIL was significantly higher in PG than in NPG cases (P<0.001). There was no difference in the mDSI distribution between the PG-/NPG-type cases. An rIL was observed in 39% (127/301) of cases, in which the location of the muscularis mucosae could not be determined or estimated and the mDIS could be estimated. In 13% (16/127) of cases, the mDSI was effective (JSCCR DSI ≥1000 and mDSI <1000 µm). Among these 16 cases, 11 (69%) did not have risk factors (mDSI, lymphovascular invasion, budding grade, or special histological types) and may have avoided unnecessary surgery.

Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer.

BACKGROUND: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability. METHODS: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists. RESULTS: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5). CONCLUSIONS: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN. TRIAL REGISTRATION: The UMIN Clinical Trials Registry Identification Number: 000004218.

Extracranial metastatic solitary fibrous tumor/hemangiopericytoma expressing G-CSF and its receptor.

Although extracranial metastases are a relatively common phenomenon in patients with solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs), factors involved in the mechanism underlying tumor growth and metastasis have not been identified. We report a case of extracranial metastatic SFT/HPC synthesizing granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor (G-CSFR). A 39-year-old man underwent a gross total resection of a well-circumscribed, dura-based, extracerebral primary tumor at the right frontal convexity. Neuropathologic evaluation of the tumor revealed an SFT/HPC characterized by staghorn vessels and a patternless architecture of hypercellular tumor cells, which had the eosinophilic cytoplasm and the nucleus immunoreactive for signal transducer and activator of transcription 6. He was treated with postoperative radiotherapy. He complained of fever and abdominal pain with systemic multiple metastatic tumors 10 years after the operation. The leukocyte count was 70,500/µL with 90.7% neutrophils (compared to 7400/µL at 39 years of age), and the serum G-CSF level was 283.0 pg/mL. Pathological examination of biopsy specimens of the liver and kidney tumors revealed the metastatic SFT/HPC. Immunohistochemically, G-CSF was localized in both the primary and metastatic SFT/HPC cells, whereas G-CSFR was localized only in the metastatic SFT/HPC cells. The tumors seemed to have the ability to produce G-CSF, even when G-CSF production is not clinically evident, suggesting that G-CSFR acquisition contributes to tumor growth, malignancy, and metastasis. In addition, there have been no reports showing G-CSF production in SFT/HPC cases. The influence of G-CSF is expected to be one of the factors related to SFT/HPC malignancy. Inhibitors of G-CSF could be a therapeutic agent for tumors that co-express both G-CSF and G-CSFR in an autocrine manner.

Association between Endoscopic Milk-White Mucosa, Epithelial Intracellular Lipid Droplets, and Histological Grade of Superficial Non-Ampullary Duodenal Epithelial Tumors.

We previously reported that superficial non-ampullary duodenal tumors (SNADETs) commonly had a whitish mucosal surface, named milk-white mucosa (MWM). The aim of this study was to evaluate the association of MWM with epithelial intracellular lipid droplets (immunohistochemically stained by adipose differentiation-related protein (ADRP)) and histological tumor grades. We reviewed endoscopic images and the histopathology of SNADETs resected en bloc endoscopically. We analyzed the correlation between the positive rates of endoscopic MWM in preoperative endoscopy and resected specimens, and ADRP-positive rates in the resected specimens. Associations between the MWM-positive rates and tumor grades, high-grade intraepithelial neoplasia (HGIN)/intramucosal carcinoma (IC), and low-grade intraepithelial neoplasia (LGIN) were analyzed. All the 92 SNADETs analyzed were <20 mm and histologically classified into 39 HGIN/IC and 53 LGIN. Spearman's rank correlation coefficient showed a significant correlation between MWM-positive and ADRP-positive rates (p < 0.001). MWM-positive rates were significantly lower in the HGIN/IC than in the LGIN in preoperative endoscopy (p < 0.001) and resected specimens (p = 0.02). Our results suggest that endoscopic MWM is closely associated with epithelial intracellular lipid droplets and that the MWM-positive rate may be a predictor of histological grade in small SNADETs.

Risk Factors Associated with the Development of Metastases in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Retrospective Analysis.

Neuroendocrine tumors develop from systemic endocrine and nerve cells, and their occurrence has increased recently. Since these tumors are heterogeneous, pathological classification has been based on the affected organ. In 2019, the World Health Organization introduced a change expected to influence neuroendocrine tumor research, as gastroenteropancreatic neuroendocrine tumors are now included within a unified classification. This retrospective study aimed to investigate the characteristics (e.g., lymph node metastases and all other metastases) of gastroenteropancreatic neuroendocrine tumors using this new classification in 50 cases. Tumor size, depth, MIB-1 index, lymphatic invasion, venous invasion, and neuroendocrine tumor grade were significantly correlated with lymph node metastasis and other metastases. The venous invasion was more strongly correlated with lymph node metastasis and all other types of metastases than with lymphatic invasion. Identification rates for lymphatic invasion were considered lower because of structural problems such as lymphatic vessels being much thinner than veins. However, venous invasion was considered effective in compensating for the low identification rate in cases of lymphatic invasion. In future research, a unified classification and standardized framework for assessment will be important when analyzing the characteristics of neuroendocrine tumors, and large-scale studies are required.

Dasatinib-induced Nonspecific Interstitial Pneumonia That Developed 7 Years after the Initiation of Dasatinib.

We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.

Hierarchical Cluster and Region of Interest Analyses Based on Mass Spectrometry Imaging of Human Brain Tumours.

Imaging mass spectrometry (IMS) has been rarely used to examine specimens of human brain tumours. In the current study, high quality brain tumour samples were selected by tissue observation. Further, IMS analysis was combined with a new hierarchical cluster analysis (IMS-HCA) and region of interest analysis (IMS-ROI). IMS-HCA was successful in creating groups consisting of similar signal distribution images of glial fibrillary acidic protein (GFAP) and related multiple proteins in primary brain tumours. This clustering data suggested the relation of GFAP and these identified proteins in the brain tumorigenesis. Also, high levels of histone proteins, haemoglobin subunit α, tubulins, and GFAP were identified in a metastatic brain tumour using IMS-ROI. Our results show that IMS-HCA and IMS-ROI are promising techniques for identifying biomarkers using brain tumour samples.

HER2 Status in Molecular Subtypes of Urothelial Carcinoma of the Renal Pelvis and Ureter.

INTRODUCTION: Erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) gene amplification or protein overexpression occurs in certain types of urothelial carcinomas. Molecular pathologic classification of urinary bladder cancer using immunohistochemistry has identified basal and luminal subtypes with differing prognoses, but the HER2 status of these subtypes has not been investigated. In addition, research on urothelial carcinoma of the renal pelvis and ureter (UCRPU) has not progressed because of its rarity, though its prognosis is worse than that of bladder cancer. In this study, we evaluated the clinical significance of HER2 status in molecular subtypes of UCRPU. MATERIALS AND METHODS: HER2 status (protein overexpression and/or gene amplification) and molecular subtyping were determined for 148 cases of UCRPU (83 and 65 cases in the renal pelvis and ureter, respectively), using immunohistochemistry and fluorescent in situ hybridization, and compared with clinicopathologic factors. RESULTS: Subtype analysis revealed that the cases were 46% basal and 54% luminal. HER2 protein overexpression and/or gene amplification was observed in 14% of UCRPU cases and was significantly more frequent in the luminal subtype than in the basal (22% vs. 4%; P = .0030). Univariate analysis showed that the overall survival of patients with HER2-positive UCRPU was significantly shorter than those with HER2-negative tumors. CONCLUSIONS: HER2 protein overexpression and gene amplification were specifically observed in the luminal subtype of UCRPU, suggesting that these cases may respond to HER2-targeted therapies like trastuzumab.

Genetic Profile and Microsatellite Instability in a Case of Secondary Esophageal Squamous Cell Carcinoma 12 Years After Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

We report on a 16-year-old Japanese boy in whom an esophageal squamous cell carcinoma (ESCC) developed 12 years after allogeneic hematopoietic stem cell transplantation was performed for aplastic anemia. A high frequency of microsatellite instability was detected in samples of ESCC. Moreover, the detection of pathogenic variants, including single nucleotide substitution of TP53 (c.346C>T) and BRCA2 (c.6952C>T) and splicing of KDM6A (c.1194+2T>G), suggest that the development of ESCC in the patient was triggered by impairment of checkpoint and repair for DNA damage and epigenetic modification through accumulation of gene mutations induced by chronic graft-versus-host disease and prolonged administration of tacrolimus.

Concurrent immunoglobulin G-lambda type multiple myeloma and mixed cellularity classical Hodgkin lymphoma: A case report.

A 66-year-old man with a swollen right inguinal lymph node (LN) had pain on the lower side of the back. Computed tomography revealed bone disease in the back and swollen right inguinal LNs. Laboratory studies showed anemia and serum immunoglobulin G-lambda (IgG-λ) type monoclonal protein. The bone marrow contained 39.6% plasma cells. He was diagnosed with IgG-λ type multiple myeloma (MM). However, the pathological findings of the right inguinal LN were mixed cellular classical Hodgkin lymphoma (HL). The administration of melphalan, prednisone, and bortezomib (MPB) was started for MM; however, swelling in the right inguinal LN increased. After three cycles of MPB, the administration of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was started for HL. However, HL was refractory to ABVD. Pancytopenia subsequently progressed and rapid swelling occurred in his LNs. He died 7 months after diagnosis. Multiple myeloma was diagnosed, based on the typical symptoms, although the pathological findings of the LN indicated a diagnosis of HL. We analyzed the molecular relationship between MM and HL cells using a direct sequencing method. The sequencing results demonstrated that the variable-diversity-joining (VDJ) region of the IgH gene was identified with 94.4% of IGLV3-32*01 in the bone marrow sample at diagnosis. Furthermore, clonotypic IgH sequence was identified in CD30-positive cells from the LN. These results suggested that the clonal HL cells were derived from the same source as the clonal MM cells and demonstrated that MM and HL in this patient may have originated from the same B cell progenitor.

Effect of Vitamin D on Relapse-Free Survival in a Subgroup of Patients with p53 Protein-Positive Digestive Tract Cancer: A Post Hoc Analysis of the AMATERASU Trial.

BACKGROUND: The AMATERASU randomized trial of vitamin D3 supplementation (2,000 IU/day; UMIN000001977) showed the potential benefit of vitamin D in a subgroup of patients with digestive tract cancer. By conducting post hoc analyses of this trial, we further explored whether subgroups stratified by expression levels of p53, vitamin D receptor (VDR), and Ki-67 modify the effect of vitamin D supplementation. METHODS: The primary outcome was relapse-free survival (RFS). On IHC using pathologic specimens, the degree of p53 protein expression parallel with TP53 missense mutations was classified as p53 positive (>10%) and p53 negative (≤10%). In addition, VDR and Ki-67 expression levels were divided into quartiles. RESULTS: The p53 status of 372 patients' pathologic specimens was evaluated. In a subgroup of patients with p53-positive cancer (n = 226), 5-year RFS was 79% in the vitamin D group, which was significantly higher than the 57% in the placebo group (HR, 0.52; 95% confidence interval, 0.31-0.88; P = 0.02). In the subgroup of patients with p53-negative cancer, 5-year RFS in the vitamin D group versus placebo group was 72% versus 84% (not significantly different), respectively. Effect modification by p53 positivity was significant (P interaction = 0.02). However, no significant effect modification by either VDR or Ki-67 was observed. CONCLUSIONS: These results generate a hypothesis that vitamin D supplementation may improve RFS in patients with p53-positive digestive tract cancer. IMPACT: The results are still preliminary, but potentially important, because TP53 is the most frequently mutated gene across cancers at all sites.

Small bowel adenocarcinoma incarcerated within an inguinal hernia.

BACKGROUND: Small bowel adenocarcinomas are rare malignant tumors that account for less than 2% of gastrointestinal malignancies. In addition, tumor incarceration in an inguinal hernia is also rare entity. We herein report a first case of small bowel adenocarcinoma incarcerated within an inguinal hernia. CASE PRESENTATION: A 75-year-old man with asymptomatic anemia (hemoglobin, 8.6 g/dl) had a checkup at our hospital. Colonoscopy revealed bleeding through the ileocecal valve and an annular stricture by a tumor in the ileum. Endoscopic biopsy revealed a well-differentiated adenocarcinoma of the small bowel. Enhanced computed tomography showed a hypervascular solid tumor incarcerated within a right inguinal hernia. With a diagnosis of small bowel adenocarcinoma incarcerated within a right inguinal hernia, the patient underwent elective laparotomy with midline excision. The small bowel tumor, located at 30 cm from the terminal ileum, was incarcerated within a right inguinal hernia, and the small bowel was adherent to the hernia sac. A 24-cm segment of the distal ileum and regional lymph nodes were resected. The hernia sac was ligated, and the bottom of the hernia sac was resected. The hernia orifice was closed by tissue repair technique via a standard oblique incision in the right inguinal region. Postoperatively, the patient remains well with no evidence of tumor or hernia recurrence as of 1 year after operation. CONCLUSIONS: We reported to our knowledge the first case of small bowel adenocarcinoma incarcerated within an inguinal hernia.

Cases Having a Gleason Score 3+4=7 With <5% of Gleason Pattern 4 in Prostate Needle Biopsy Show Similar Failure-free Survival and Adverse Pathology Prevalence to Gleason Score 6 Cases in a Radical Prostatectomy Cohort.

Recent discussions have suggested expanding the inclusion criteria for active prostate cancer surveillance to include cases with a Gleason score (GS) of 3+4=7. In this study, we examined this proposed use of a limited percent Gleason pattern 4 (%GP4) to identify candidates of active surveillance among 315 patients who underwent radical prostatectomy for prostate cancer with a GS of 6 or 3+4=7 via needle biopsy. The latter cases were divided into 4 groups using highest or overall %GP4 cut-off values of 5% and 10% as determined from prostate needle biopsies. The frequency of adverse pathology and risk of biochemical recurrence were compared between the GS 6 and both GS 3+4=7 groups. Adverse pathology was defined as a GS 4+3=7 or higher, pT3b staging or positive lymph node metastasis. Notably, the Gleason pattern 4 <5% and GS 6 groups did not differ significantly in terms of the frequency of adverse pathology and risk of biochemical recurrence by the highest method. However, other highest Gleason pattern 4 categories had significantly higher frequencies and risks. Using the overall method, even the Gleason pattern 4 <5% group had a significantly higher frequency of adverse pathology and risk of biochemical recurrence relative to the GS 6 group. In conclusion, our findings suggest that patients with a GS 3+4=7 on biopsy with a highest %GP4 <5% are similar candidates for active surveillance to men with GS 6 cancers.